Research Projects

Bone repair and regeneration is a well-defined series of molecular signaling pathways of bone induction and conduction events to restore skeletal function. The urgent need for innovative solutions is driven by the substantial burden on healthcare resources caused primarily by traumatic bone injuries, osteoporosis, and osteolytic bone metastases. Clinically approved strategies for non-unions broadly include osteoinductive and osteoconductive-based therapies, however, both strategies showed limited fracture healing and vascularization and need further surgeries. The systemic administration of fracture-targeting bone anabolics represents a great potential for improving treatment outcomes in bone healing. Osteogenic-specific peptides such as enamel matrix derivatives have shown bone regeneration, however, large molecular weight, immunogenicity, and instability in vivo, limit their practical applications. On the other hand, owing to the outstanding osteo-conductivity/inductivity properties, hydroxyapatite (HAp) biomaterials have attracted considerable research for artificial bone, bone implants, and coatings. This opens an era to design HAp-peptide-based composites. Nevertheless, their key weaknesses are brittle nature, structural instability, and weak interfacial integration. This bottleneck may be circumvented by utilizing porous compounds like zeolites-like metal-organic frameworks (ZMOF) due to their unprecedented porosity, ultrahigh surface areas, cytoprotective, and significant thermal and chemical stability. Our central hypothesis is based on the peptides with high binding affinity to HAp, and if peptide -HAp interactions are more energetically favourable, they can bind strongly to osteogenic progenitor cells and influence osteoblast adhesion, migration, proliferation, differentiation, and ECM signaling. Additionally, ZIF-8 based MOFs can provide sustained release of Zn2+, which is actively involved in osteogenesis, angiogenesis, and antibacterial processes. Thus, our goal is to fabricate and characterize a new composite biomaterial composed of HAp-peptide/ZIF-8-based MOF as a therapeutic strategy through systemic mode to accelerate bone repair and reduced toxic side-effects. For this, first, we will identify the (HAp)-binding peptide motifs in enamel matrix proteins and their molecular mechanisms of interactions by molecular dynamics simulations. Next, we will redesign these (HAp)-binding peptides, and will then be grafted onto HAp. As peptides are highly susceptible to chemical degradation and low mechanical strength of HAp, we will functionalize them with ZIF-8 into nanocomposite materials, which could provide a microenvironment for simultaneous bone repair and regeneration. These ZMOF/HAp-Peptide composites with different peptide sequences will be then screened for cytocompatibility, osteoblast proliferation, and differentiation, and, finally, in vivo, proof of concept will be evaluated in animal models to meet commercialization strategy.